WO2020041200A1 - Formes solides de benzoxaborole substitué et compositions associées - Google Patents

Formes solides de benzoxaborole substitué et compositions associées Download PDF

Info

Publication number
WO2020041200A1
WO2020041200A1 PCT/US2019/047073 US2019047073W WO2020041200A1 WO 2020041200 A1 WO2020041200 A1 WO 2020041200A1 US 2019047073 W US2019047073 W US 2019047073W WO 2020041200 A1 WO2020041200 A1 WO 2020041200A1
Authority
WO
WIPO (PCT)
Prior art keywords
crystalline form
compound
formulation
type
agrochemical composition
Prior art date
Application number
PCT/US2019/047073
Other languages
English (en)
Inventor
Chun Yu LIU
Marissa Caroline AUBREY
Yong-Kang Zhang
Michael Samuels
Original Assignee
Boragen Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Boragen Inc. filed Critical Boragen Inc.
Priority to AU2019325436A priority Critical patent/AU2019325436B2/en
Priority to EP19852023.1A priority patent/EP3836938A4/fr
Priority to CA3148168A priority patent/CA3148168A1/fr
Priority to CN201980067966.8A priority patent/CN112867494A/zh
Priority to JP2021532287A priority patent/JP2021534247A/ja
Priority to MX2021001904A priority patent/MX2021001904A/es
Priority to BR112021003037-9A priority patent/BR112021003037A2/pt
Publication of WO2020041200A1 publication Critical patent/WO2020041200A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
    • A01N55/08—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur containing boron
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/12—Powders or granules
    • A01N25/14—Powders or granules wettable
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Definitions

  • the present disclosure relates to solid forms of a substituted benzoxaborole compound, specifically a crystalline form of a compound of formula (I),
  • compositions comprising a crystalline form of the compound of formula (I), and methods of its use.
  • Boron is a unique, and often misconstrued, element of the periodic table due to its powerfully effective and unpredictable biological properties.
  • Initial innovation in the field of boron chemistry was impaired due to the incapacity to prepare pure boron, especially in its crystalline form.
  • boron-containing molecules such as oxaboroles and benzoxaboroles demonstrate use as antimicrobials (see WO 2016/128949, U.S. Patent No. 9,617,285, and WO 2016/164589).
  • the duplicitous nature of boron-containing compounds places their activities on a broad continuum ranging from highly toxic to exceptionally benign.
  • benzoxaborole is in a dynamic equilibrium between the neutral trigonal planar state and the ionic tetrahedral state (illustrated in Scheme 1), that can vary drastically depending on the specific environment the benzoxaborole is located in.
  • a solid form of the benzoxaborole active ingredient adds an additional layer of complexity to the formulation of benzoxaborole active ingredients.
  • a solid form selected for formulation development can be critical where multiple solid forms exist. Solid forms share an identical chemical formula, but differ in their three-dimensional structure. Additionally, their respective physio-chemical properties including crystal shape, hardness, color, melting point, hydroscopicity, density, solubility, dissolution, dissolution rate, suspensibility, thermodynamic stability, mechanical stability, physical and chemical stability, melting behavior, dissolution rate, and biological availability can vary drastically.
  • Such variations in the physio-chemical properties can have a drastic effect on the development of the active ingredient and/or formulation of the active ingredient; by choosing the correct solid form, better processing conditions, improved dissolution profile, increased stability, and increased shelf life, for example, can be achieved.
  • the selection of the correct solid form is key; the recrystallization of a less stable form can affect the properties of the formulated product, resulting in a product that is not useable.
  • variations in the solid form may also allow for lower effective rates of use (i.e. it is possible to lower the fungicidally effective amount) by improving bioavailability.
  • use of the other solid forms may lead to the inability to create efficacious formulations.
  • a solid form chosen for further development should have properties, which make it more advantageous relative to another solid form (crystalline form or an amorphous form) of the same compound.
  • the physical, chemical, and biological properties of a solid form can have a significant effect on the development of production methods and formulations.
  • predicting whether the solid state of a compound may be present as more than one solid form, or the number of forms is not possible, nor is it possible to predict the properties of any of these forms (e.g. crystalline form or amorphous form).
  • active ingredient must be screened to determine the number of solid forms available and the solid forms must be then tested as one cannot predict which solid form will confer advantageous properties.
  • a suspension concentrate (SC) formulation may be preferred over an emulsion concentrate (EC) formulation because the lack of organic solvent in SC formulations often leads to a less phytotoxic formulation relative to EC formulations.
  • SC suspension concentrate
  • EC emulsion concentrate
  • unwanted crystal growth or recrystallization can occur during storage or during application. Such crystal growth is detrimental as it leads to, among others, the thickening and potential solidification of the formulation, leading to blockages in application equipment (e.g., in spray nozzles or in agricultural application machinery) as well as uneven application.
  • the amorphous form may be the most soluble solid form, it can recrystallize as another solid form and destroy the formulated product, rendering the product unusable.
  • Solid forms that are hydrates and solvates can lose their solvent or water during the milling process, or solvates/hydrates can be formed during the milling process, either of which may lead to unstable formulations. Additionally, the solubility of a specific solid form may affect what formulation type is selected for commercialization. The discovery, identification, and use of stable solid forms suitable for the specific intended application can overcomes these issues.
  • Solid active ingredients may be screened for their structures by conventional methods known in the art. For example, one characterization includes the use of X- ray powder diffraction (XRPD).
  • DSC differential scanning calorimetry
  • TGA thermogravimetric analysis
  • IR Raman or infrared spectroscopy
  • HPLC high-pressure liquid chromatography
  • an active ingredient such as a benzoxaborole
  • an active ingredient such as a benzoxaborole
  • the present disclosure relates to a crystalline form of a compound of formula I:
  • the crystalline comprises a Crystalline Form A.
  • the crystalline form consist essentially of Crystalline Form A.
  • the Crystalline Form A is substantially free from impurities.
  • the present disclosure relates to a compound Crystalline Form A of 5-chlorobenzo[c][ l ,2]oxaborol- 1 (3//)-ol.
  • the present disclosure relates to a compound Crystalline Form A of 5- chlorobenzo[c][ l ,2]oxaborol- l (3//)-ol characterized by an X-ray diffraction pattern (XRPD) comprising one or more 2Q angle value selected from: about l6° ⁇ 1.0, about 23° ⁇ 1.0, about 25° ⁇ 1.0 , and about 27° ⁇ 1.0.
  • the Crystalline Form A is characterized by two or more of the listed 2Q angle values.
  • the Crystalline Form A is characterized by three or more of the listed 2Q angle values.
  • the Crystalline Form A is characterized by all four of the listed 2Q angle values.
  • Crystalline Form A of 5- chlorobenzo[c][ l ,2]oxaborol- 1 (3//)-ol having a powder X-ray diffraction pattern substantially the same as Figure 25.
  • Another aspect described herein is a compound Crystalline Form A of 5- chlorobenzo[c][ l ,2]oxaborol- l (3//)-ol characterized by an onset temperature of 142.7 °C.
  • Another aspect described herein is a compound Crystalline Form A of 5- chlorobenzo[c][ l ,2]oxaborol- l (3//)-ol characterized by weight loss of 0.5% up to l00°C.
  • the compounds described herein further comprises wherein the crystalline form is coated by an adjuvant, a wetting agent, a dispersing agent, an agriculturally acceptable polymer, an inert solid or any combination thereof.
  • the compounds described herein characterized by a particle size Dso of between (i) about 3.00 pm to about 10.50 pm, (ii) about 3.00 pm to about 7.50 pm, (iii) about 3.00 pm to about 6.50 pm, (iv) about 4.00 pm to about 6.50 pm, or (v) about 4.50 pm to about 6.00 pm.
  • the compounds described herein characterized by a particle size D90 of between (i) about 1.00 pm and about 10.00 pm, between (ii) about 7.00 pm to about 30.00 pm, (iii) about 14.00 pm to about 30.00 pm, (iv) about 15.00 pm to about 30.00 pm, (v) about 15.00 pm to about 22.00 pm, or (vi) about 15.00 pm to about 18.00 pm.
  • an agrochemical composition comprising the compounds described herein and at least one agriculturally acceptable carrier.
  • the agrochemical composition further comprises at least one other active ingredient.
  • the agrochemical composition is an emulsifiable concentrate, a dust, a suspension concentrate, a wettable powder, granule, or a seed treatment.
  • the emulsifiable concentrate comprises up to about 95% compound; up to about 30% surface-active agent; and up to about 80% liquid carrier.
  • the dust comprises up to about 10% compound; and up to about 99.9% solid carrier.
  • the suspension concentrate comprises up to about 75% compound; up to about 94% water; and up to about 10% dispersing and wetting agent.
  • the wettable powder comprises: up to about 90% compound; up to about 20% surface-active agent; and up to about 95% solid carrier.
  • the granule comprises: up to about 30% compound; and up to about 99.9% solid carrier.
  • agrochemical composition described herein comprises an effective amount of compound for preventing or controlling microbial infections on plants or plant propagation material.
  • the agrochemical composition further comprises at least one additional active ingredient.
  • the mixture is a synergistic mixture.
  • the microbial infection is a fungal infection.
  • the at least one additional active ingredient is selected from the group consisting of: a fungicide, nematicide, insecticide, antimicrobial, or any combination thereof.
  • Another aspect described herein is a method of preparing an agrochemical formulation comprising dissolving an antimicrobially effective amount, when used either alone or as a mixture with at least one additional active ingredient, of any of the compounds described herein.
  • Another aspect described herein is a method of controlling microbial infection on plants or plant propagation material comprising treating the plant or the plant propagation material with a antimicrobially effective amount of any of the compound described herein.
  • the methods described herein comprise a single treatment or multiple treatments.
  • Another aspect described herein is a method of preparing an agrochemical formulation comprising dissolving an antimicrobially effective amount of any of the compounds described herein in at least one liquid carrier.
  • the methods described herein further comprise at least one additional active ingredient to form a mixture.
  • the mixture is a synergistic mixture.
  • the formulation is used to treat a microbial infection.
  • the microbial infection is a fungal infection.
  • the at least one additional active ingredient is selected from the group consisting of:
  • Another aspect described herein is a method of preventing or controlling microbial infection on plants or plant propagation material comprising treating the plant or the plant propagation material with an antimicrobially effective amount of any of the compounds described herein.
  • Another aspect described herein is a method for preparation of any of the compounds described herein comprising the steps of anti-solvent addition, reverse anti-solvent addition, slow evaporation, slow cooling, slurry at room temperature, slurry at elevated temperature, slurry cycling, vapor-solid diffusion, vapor-solution diffusion, or polymer induced crystallization.
  • the slow cooling is performed in a mixture of isopropyl acetate and ethyl acetate.
  • the anti-solvent addition is performed in l,4-dioxane and water.
  • Figure 1 A shows XPRD patterns of starting material
  • Figure 1B shows TGA/DSC curves of starting material
  • Figure 2A shows DVS plot of starting material
  • Figure 2B shows an XRPD overlay of starting material before and after DVS; [0033] Figure 3A shows an XRPD overlay of anti-solvent addition experiments; [0034] Figure 3B shows an XRPD overlay of anti-solvent addition experiments; [0035] Figure 4A shows an XRPD overlay of anti-solvent addition experiments; [0036] Figure 4B shows an XRPD overlay of reverse anti-solvent addition
  • Figure 5A shows an XRPD overlay of reverse anti-solvent addition
  • Figure 5B shows an XRPD overlay of reverse anti-solvent addition
  • Figure 6A shows an XRPD overlay of slow evaporation experiments
  • Figure 6B shows an XRPD overlay of slow evaporation experiments
  • Figure 7A shows an XRPD overlay of slow evaporation experiments
  • Figure 7B shows an XRPD overlay of slow cooling experiments
  • Figure 8A shows an XRPD overlay of slow cooling experiments
  • Figure 8B shows an XRPD overlay of slurry at room temperature experiments
  • Figure 9A shows an XRPD overlay of slurry at room temperature
  • Figure 9B shows an XRPD overlay of slurry at room temperature experiments
  • Figure 10A shows an XRPD overlay of slurry at room temperature
  • Figure 10B shows an XRPD overlay of slurry at 50 °C experiments
  • Figure 11 A shows an XRPD overlay of slurry at 50 °C experiments
  • Figure 11B shows an XRPD overlay of slurry cycling (50-5 °C) experiments
  • Figure 12A shows an XRPD overlay of slurry cycling (50-5 °C) experiments
  • Figure 12B shows an XRPD overlay of vapor-solid diffusion experiments
  • Figure 13A shows an XRPD overlay of vapor-solid diffusion experiments
  • Figure 13B shows an XRPD overlay of vapor-solid diffusion experiments
  • Figure 14A shows an XRPD overlay of vapor-solution diffusion experiments
  • Figure 14B shows an XRPD overlay of vapor-solution diffusion experiments
  • Figure 15A shows an XRPD overlay of polymer induced crystallization experiments
  • Figure 15B shows an XRPD overlay of polymer induced crystallization experiments
  • Figure 16A shows an XRPD overlay of evaporation induced crystallization experiments
  • Figure 16B shows an XRPD overlay of pH modification induced
  • Figure 17A shows an XRPD overlay of crystallization experiments with the presence of cations
  • Figure 17B shows an XRPD overlay of the presence of NaCl induced crystallization experiments
  • Figure 18A shows an XRPD overlay of the presence of KC1 induced crystallization experiments
  • Figure 18B shows an XRPD overlay of the presence of AlCh induced crystallization experiments
  • Figure 19A shows the asymmetric unit of (I) single crystal
  • Figure 19B shows thermal ellipsoid drawing of the (I) molecule (at 50% probability level);
  • Figure 20A shows the unit cell of (I) from the single crystal structure
  • Figure 20B shows classic hydrogen-bonds in the (I) single crystal structure
  • Figure 21A shows calculated and experimental XRPDs of the single crystal sample and XRPD of (I) Type A reference;
  • Figure 21B shows VT-XRPD patterns of crystalline form A
  • Figure 22A shows an XRPD overlay of heating experiment for crystalline form A
  • Figure 22B shows an 'H NMR overlay of crystalline form A before and after heating
  • Figure 23A shows TGA curves of crystalline form A before and after heating
  • Figure 23B shows TGA curve of crystalline form A
  • Figure 24A shows Cycle TGA curve of crystalline form A
  • Figure 24B shows isothermal TGA curve of crystalline form A
  • Figure 25 shows a full XRPD pattern of crystalline form A
  • Figure 26A shows an XRPD of starting material
  • Figure 26B shows an XRPD of milled and formulated material
  • Figure 27A shows an overlay of milled and formulated material and crystalline Form A for reference
  • Figure 27B shows an XRPD of starting material
  • Figure 28A shows an XRPD of milled and formulated material
  • Figure 28B shows an overlay of milled and formulated material and crystalline Form A for reference
  • Figure 30A shows an overlay of milled and formulated material
  • Figure 30B shows an XRPD sample of starting material
  • Figure 31A shows an overlay of milled and formulated material
  • Figure 31B shows an shows an overlay of milled and formulation material
  • Figure 32A shows an XRPD of starting material
  • Figure 32B shows an XRPD of milled and formulated material
  • Figure 33A shows an overlay of milled and formulation material and crystalline Form A for reference.
  • the phrase“True Fungi” is used herein for all of the organisms discussed herein except for the Oomycota (such as Pythium , Phytophthora and Plasmopard).
  • the term“fungi” or“fungus” is used to include all of the organisms discussed herein, including the Oomycota.
  • “pesticidal” means the ability of a substance to increase mortality or inhibit the growth rate of plant and/or animal pests.
  • the term is used herein, to describe the property of a substance/active ingredient to exhibit activity against microbes, insects, arachnids, parasites, and/or other pests.
  • a substance that is pesticidal is a“pesticide”.
  • pathogen and“pest” are used interchangeably herein to broadly include any organism that may be harmful to the entity to which a contemplated compound or composition containing such a compound is administered.
  • pathogen or“pest” is intended to include a microbe, an insect, an arachnid, or a parasite, or other organism that may cause infection or disease directly or as a vector, as well as any combinations thereof.
  • Plant pests are commonly nematodes, insects, arachnids, bacteria, viruses, or fungi, or combinations thereof. Insect and arachnid pests of plants often eat one or more portions of a plant, plant parts, plant propagation materials, and/or harvested fruits or vegetables.
  • the term“health of a plant” or“plant health” is defined as a condition of the plant and/or its products. As a result of the improved health, yield, plant vigor, quality and tolerance to abiotic or biotic stress may be increased.
  • the term“fungicide” and“fungicidal” as used herein, refers to the ability of a substance or composition to increase mortality of, control, inhibit, or ameliorate the growth rate of fungi.
  • microbe is intended to include any microscopic organism that is harmful to the entity to which a contemplated compound or composition containing such is administered.
  • microbe is intended to include fungi, bacteria, and viruses, as well as any combinations thereof.
  • antimicrobial and“antimicrobially” as used herein, refers to the ability of a substance or composition to increase mortality of, control, inhibit, or ameliorate the growth rate of microbes, particularly fungi.
  • the term“effective amount”, as used herein means the quantity of such a compound, composition, active ingredient, or a combination of such compounds, compositions, or active ingredients to provide the desired local or systemic effect.
  • the amount that is capable of killing, controlling, infecting fungi, retarding the growth or reproduction of microbes (particularly fungi), reducing a microbe (e.g. a fungal) population, and reducing damage to plants caused by microbes (e.g. fungi) is a fungicidally effective amount.
  • Agriculturally acceptable carrier can be a solid or a liquid, or any carriers known in the art that are suitable for agricultural applications including solvents that dissolve or suspend the active ingredient, carriers added to a pesticide product to aid in the delivery of the active ingredient, or adjuvants to allow the pesticide to stick to or spread out on the application surface (i.e., leaves). Other adjuvants aid in the mixing of some formulations when they are diluted for application. Additional information concerning carriers can be found in Label Review Manual ; U.S.
  • agriculturally acceptable excipient is conventionally known to mean agriculturally acceptable carriers used in formulating compositions effective for the desired use.
  • carrier is used herein to denote a natural or synthetic, organic, or inorganic material that constitutes a portion of a diluent medium in which the active ingredient (e.g. a benzoxaborole) is dispersed or dissolved.
  • This carrier is inert and agriculturally acceptable, in particular to the plant being treated.
  • the phrase “agriculturally acceptable” is utilized herein to be analogous to“pharmaceutically acceptable” as used in pharmaceutical products to describe diluent media.
  • a carrier can be solid (clays, natural or synthetic silicates, silica, resins, waxes, solid fertilizers, and the like) or liquid (water, alcohols, ketones, petroleum fractions, aromatic or paraffinic hydrocarbons, chlorinated hydrocarbons, liquefied gases, and the like).
  • carriers may be solid or liquid.
  • the carrier is a liquid and the liquid is water.
  • formulation and“agrochemical composition” are used interchangeably and refer to a solid or liquid mixture containing a benzoxaborole derivative and agriculturally acceptable carriers, adjuvants, wetting agents, dispersants, surfactants, and the like. Formulation refers both to concentrated formulations and diluted or applied formulations depending on the desired
  • Formulations comprise both the concentrated as well as applied formulations.
  • formulations include: wettable powders (WP), water dispersable granules (WG or WDG), soluble concentrates (SL), suspension concentrates (SC), emulsifiable/emulsion-concentrates (EC), concentrated aqueous emulsions (EW), microemulsions (ME), suspoemulsion (SE), oil dispersions (OD), microencapuslted particles (CS), soil applied granule on inters or fertilizer carriers (GR), emulsions, suspensions, pre-mixes, tank-mixes, and dosage formulations, etc.
  • WP wettable powders
  • WG or WDG water dispersable granules
  • SL soluble concentrates
  • SC suspension concentrates
  • EC emulsifiable/emulsion-concentrates
  • EW concentrated aqueous emulsions
  • ME microemulsions
  • SE suspoemulsion
  • plant propagation material means seeds of all kinds including fruits, tubers, bulbs, grains, cuttings, and cut shoots.
  • the term“cultivars and plant varieties”, as used herein, means plants obtained by conventional propagation and breeding methods which can be assisted or supplemented by one or more biotechnological methods such as the use of double haploids, protoplast fusion, random and directed mutagenesis, molecular or genetic markers, or the use of bioengineering and genetic engineering.
  • plant parts means all above ground and below ground parts and organs of plants such as shoot, leaf, blossom, root, leaves, needles, stems, branches, blossoms, fruiting bodies, fruits and seed, roots, corms, seeds, and rhizomes. Crops, vegetative, and generative propagating materials such as cuttings, corms, rhizomes, runners, and seeds also belong to plant parts.
  • plant-strengthening or resistance-inducing substances means the substances or combinations of substances capable of stimulating the defense system of plants in the manner that, when subsequently inoculated with unwanted phytopathogenic fungi, microorganisms, and viruses, the treated plants display a substantial degree of resistance to these phytopathogenic fungi, microorganisms, and viruses.
  • solid form of a chemical compound, active ingredient, or composition thereof encompasses amorphous forms and crystalline forms.
  • a crystalline form of a compound contains the constituent molecules arranged in orderly repeating patterns extending in all three spatial dimensions.
  • an amorphous solid form has no long-range order in the position of molecules.
  • the present disclosure has several benefits and advantages.
  • the present disclosure relates to an advantageous crystalline form of a compound of formula (I):
  • US 2016/0324160 discloses that certain benzoxaborole compounds and compositions thereof have antimicrobial activity, specifically anti-fungal activity.
  • the compound of formula (I) is disclosed:
  • the present disclosure relates to a crystalline form of a compound of formula (I):
  • the crystalline form A may be characterized by the unit cell parameters of its single crystal as shown in Table A. This solid form, referred to herein as“crystalline form A” or“the crystalline form” or“Type A” was obtained by methods described in Examples 1-3.
  • the crystalline form A may also be characterized by an X-ray powder diffraction pattern expressed in terms of 2Q angles or d spacings.
  • the crystalline form A has an X-ray powder diffraction pattern comprising 2Q angles at values of about 16°, 23°, 25°, and 27°.
  • a full list of 2Q angles and d spacings are in Example 6. The values are generated using the instrument parameters detailed in Example 1.
  • Crystalline form A was formed under several screening conditions, demonstrating that it was a robust solid form across a wide array of solvents and conditions. Accordingly, crystalline form A, the crystalline form of the disclosure, was selected for further development, since crystalline forms are considered advantageous for the reasons outlined above.
  • the crystalline form of the disclosure, crystalline form A may be coated by an adjuvant, a wetting agent, a dispersing agent (also referred to herein as a dispersant), or absorbed to an agriculturally acceptable polymer, or an inert solid or any combination thereof.
  • a dispersing agent also referred to herein as a dispersant
  • the crystalline form of such a composition is able to be identified by the same methods as the uncoated form crystalline form using methods herein described.
  • the crystalline form of the disclosure may be applied in its unchanged form, but is more preferably incorporated into an agrochemical composition.
  • the disclosure provides an agrochemical composition comprising the crystalline form of the disclosure as defined above and at least one agriculturally acceptable carrier. It is contemplated, due to the compound's biological activity, that the crystalline form of the disclosure may also be incorporated into pharmaceutical compositions.
  • the disclosure disclosed herein also includes an agrochemical composition comprising: a crystalline form of the compound of formula
  • the agrochemical composition may be, for example, an
  • EC emulsifiable concentrate
  • SC suspension concentrate
  • WP wettable powder
  • WDG water dispersible granule
  • the emulsifiable concentrate comprises, for example: 1-50% dissolved crystalline form A, 1 to 30% surface-active agent; and 20 to 98% liquid carrier.
  • the emulsifiable concentrate is 5-50% dissolved crystalline form A, 5-10% surface-active agent, and 40-90% liquid carrier.
  • the agrochemical composition is a dust, wherein the dust comprises, for example: 0.1% to 10% crystalline form A and 99.9 to 90% solid carrier.
  • the agrochemical composition is a suspension concentrate, wherein the suspension concentrate comprises, for example crystalline form A, dispersing agent, wetting agent, rheology modifier, anti-freeze, anti-foam, biocide, and water.
  • An exemplary formulation comprises: about 20-70% crystalline form A, about 0.5-10% dispersing/wetting agent, about 0.1-0.5% rheology modifier, about 0.1-10% antifreeze, about 0.1-0.5% antifoam, about 0.05-0.2% biocide, with the remainder of the SC formulation comprising water.
  • a contemplated SC formulation further comprises an adjuvant.
  • the agrochemical composition is a wettable powder, wherein the wettable powder comprises, for example: 0.5 to 90% crystalline form A and 0.5 to 20% wetting agents and dispersants with the remainder of the wettable powder formulation comprising a solid carrier.
  • the wettable powder comprises: 10-90% crystalline form A, 1-3% wetting agent, and 2- 5% dispersant, with the remainder of the wettable powder formulation comprising a solid carrier.
  • the agrochemical composition is a granule (for example, a water dispersible granule), wherein the granule comprises, for example:
  • the agrochemical composition is a seed treatment, wherein the seed treatment comprises, for example: crystalline form A, and one or more of a dispersing agent, a wetting agent, a rheology modifier, an anti freeze, a biocide, a binder/film former system, a coloring agent, and optionally other property modifiers. Seed treatment formulations are commonly made from pre- prepared suspension concentrate formulations.
  • the agrochemical composition comprises an antimicrobially effective amount of crystalline form A for preventing or controlling microbial infection on plants or plant propagation material.
  • the agrochemical composition comprises a fungicidally effective amount of crystalline form A for preventing or controlling fungal infection on plants or plant propagation material.
  • the present disclosure also encompasses a method of preparing an agrochemical composition comprising dissolving an antimicrobially effective amount of a crystalline form of the compound of formula (I):
  • the agrochemical composition comprises less than an effective amount.
  • the antimicrobially effective amount is a fungicidally effective amount.
  • the agrochemical composition is an emulsion concentrate.
  • the agrochemical composition can further comprise a second liquid carrier(s).
  • the liquid carrier and/or the second liquid carrier is an organic solvent, a protic solvent, an aprotic solvent, an oil, or any combinations thereof.
  • the agrochemical composition may additionally comprise, for example, emulsifiers such as surface active agents (surfactants), ionic surfactants, non-ionic surfactants, and adjuvants.
  • the present disclosure also encompasses a method of preparing an agrochemical composition comprising suspending an antimicrobially effective amount of a crystalline form of the compound of formula I:
  • the crystalline form is crystalline Form A, in at least one carrier.
  • the carrier can be a solid or a liquid.
  • the agrochemical composition comprises less than an effective amount.
  • the antimicrobially effective amount is a fungicidally effective amount.
  • the agrochemical composition is a suspension concentrate.
  • the suspension concentrate comprises a liquid carrier and the liquid carrier is water.
  • Such a suspension concentrate may additionally comprise, for example, dispersing agents and wetting agents.
  • Suspension concentrate formulations may be used to prepare additional formulations such as seed treatment formulations. Accordingly, another aspect of the disclosure is a seed treatment formulation wherein a seed is coated with an
  • agrochemical composition comprising a crystalline form of the compound of formula I:
  • the formulations/agrochemical compositions described herein may comprise a carrier and may be conveniently formulated in a known manner into emulsifiable concentrates, suspension concentrates, coatable pastes, directly sprayable or dilutable solutions, emulsions, wettable powders, soluble powders, dusts, granulates, and/or encapsulations in polymeric substances.
  • the carrier can be any solid carrier or a liquid carrier known in the art suitable for agrochemical
  • compositions are chosen based on objectives and the circumstances.
  • a contemplated composition can contain adjuvants such as stabilizers, antifoams, viscosity regulators, binders, or tackifiers, fertilizers, micronutrient donors, additives that enhance plant uptake, spreaders, stickers, or other compositions for obtaining special effects.
  • adjuvants can be included in the agrochemical composition/formulation or tank mixed with the agrochemical composition/formulation prior to application.
  • Suitable carriers and adjuvants can be either solid or liquid and are substances in formulation technologies such as natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders, or fertilizers.
  • the diluent media as described in WO 97/33890, is incorporated by reference. Water-based diluent media are preferred.
  • Contemplated formulations include any conventional formulation such a powder, an emulsion, a flowable concentrate, a solution, a water dispersible powder, a capsule suspension, a gel, a cream, an emulsion concentrate, a suspension concentrate, a suspo-emulsion, a capsule suspension, a water dispersible granule, an emulsifiable granule, a water in oil emulsion, an oil in water emulsion, a micro- emulsion, an oil dispersion, an oil miscible liquid, a soluble concentrate, an ultra-low volume suspension, an ultra-low volume liquid, a technical concentrate, a dispersible concentrate, a wettable powder, a suspension, or any technically feasible formulation.
  • Crystalline form A compositions of the current disclosure can be produced by one skilled in the art through mixing the crystalline form A with appropriate formulation inerts such as solid or liquid carriers and additional ingredients such as surface-active compounds (surfactants), biocides, anti-freeze agents, stickers, thickeners, and compounds that provide adjuvant effects and the like.
  • appropriate formulation inerts such as solid or liquid carriers
  • additional ingredients such as surface-active compounds (surfactants), biocides, anti-freeze agents, stickers, thickeners, and compounds that provide adjuvant effects and the like.
  • surfactants surface-active compounds
  • biocides biocides
  • anti-freeze agents stickers
  • thickeners and compounds that provide adjuvant effects and the like.
  • conventional slow release formulations can be employed where long- lasting efficacy is intended.
  • Formulations to be applied in spraying forms such as emulsion concentrates, water dispersible granules, wettable powders, granules, and suspension concentrates can contain surfactants, wetting agents, dispersing agents, and optionally other compounds that provide adjuvant effects.
  • a commercial product of the agrochemical composition is preferably formulated as a concentrate (an agrochemical composition), and the end user normally employs a diluted formulation or an applied formulation for administration to the plants of interest.
  • a diluted formulation or dilution composition is referred to as a tank-mix composition or an applied formulation.
  • a tank-mix composition or applied formulation is prepared by diluting a formulation comprising crystalline form A with a carrier such as water and also can contain further auxiliaries as an option. However, an aqueous tank-mix is preferred.
  • Each of the above formulations can be prepared as a package containing the crystalline form of the disclosure together with other ingredients of the formulation (carriers, diluents, emulsifiers, surfactants, wetting agents, dispersing agents, etc.).
  • the formulations can also be prepared by a tank mix method, in which the ingredients are obtained separately and combined at the grower site.
  • These formulations can be applied to the areas where control is desired by conventional methods.
  • Dust and liquid formulations for example, can be applied by the use of power-dusters, broom and hand sprayers and spray dusters.
  • the formulations can also be applied from airplanes as a dust, a spray, or by rope wick applications. Both solid and liquid formulations may also be applied to the soil in the locus of the plant to be treated, allowing the active ingredient to penetrate the plant through the roots.
  • the formulations of the disclosure may be used for dressing applications/seed treatments on plant propagation material to provide protection against microbial infections such as fungal infections on the plant propagation material as well as against microbes (particularly fungi) occurring in the soil.
  • the compound of formula (I) may be applied to plant propagation material to be protected by impregnating the plant propagation material, in particular, seeds, either with a liquid formulation (e.g. an SC) of the crystalline form A.
  • SC liquid formulation
  • other types of applications are possible, for example, the specific treatment of plant cuttings or twigs serving as propagation materials.
  • the agrochemical e.g. an SC
  • compositions and formulations of the present disclosure are applied prior to disease pressure.
  • Suitable surface-active compounds are non-ionic, or ionic surfactants (cationic and/or anionic), and have good emulsifying, dispersing and wetting properties.
  • surfactants is also to be understood as meaning mixtures of at least one surfactant.
  • surfactant includes wetting agents and dispersing agents, and other compounds that provide adjuvancy effects.
  • Preferred non-ionic surfactants include, but are not limited to, high molecular weight polymers, polycondensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty amines, substituted phenols (in particular alkylphenols or arylphenols such as mono- and di-(polyoxyalkylene alkylphenol), polycondensates of ethylene oxide with phosphated tristyrylphenols and polycondensates of ethylene oxide with phosphoric esters of alcohols or phenols, amine ethoxylates, castor oil ethoxylates and polyethylene glycol derivatives of hydrogenated castor oil, sorbitan fatty acid ester ethoxylates, sorbitan fatty acid esters, non-ionic ethoxylates, branched and unbranched secondary alcohol ethoxylates, nonylphenol ethoxylates, octylphenol ethoxylates, fatty alcohol eth
  • Preferred ionic surfactants include, but are not limited to, alkyl ether phosphates, alkyl phenol ether phosphates, alkyl phenol ether sulphates, condensed naphthalene sulfonates and salts, sodium alkyl naphthalene sulphonate blends, sodium naphthalene sulphonate condensate, aromatic hydrocarbon sulfonic acids, aromatic hydrocarbon sulfonic salts, aromatic hydrocarbon sulfonic blends, fatty alcohol sulphates, alkyl ether carboxylic acids, alkyl ether carboxylic salts, alkyl ether sulphates, monosulphosuccinates, polysulphosuccinates, alkyl phosphates, alkyl benzene sulphonic acids, alkyl benzene sulphonic salts, lignosulphonates and salts, alkylaryl sulphonates, alkyl
  • the surfactant is at least one of a fatty alcohol ethoxylate, alkyl phenol ethoxylate, castor oil based ethoxylate, fatty acid etoxylate, EO-PO block co-polymer, acrylic co-polymer, styrene acrylic polymer, sorbitan(ol) ester ethoxylate, sarcosinate, alkyl polysaccrharide, alkyl amine ethoxylate, amine oxide, siliconics, graft and/or comb polymer (ethoxylated or propoxylated and non ethoxylated), alkyl ether phosphate, alkyl phenol ether phosphate, alkyl phenol ether sulphate, condensed naphthalene sulfonate and/or salt, sodium alkyl naphthalene sulphonate blend, sodium naphthalene sulphonate
  • the surfactant is at least one of a(n): amine ethoxylates, alkylaryl sulphonates, alkylbenzene sulphonates, castor oil ethoxylates and polyethylene glycol derivatives of hydrogenated castor oil, sorbitan fatty acid ester ethoxylates, sorbitan fatty acid esters, non-ionic ethoxylates, branched and unbranched secondary alcohol ethoxylates, nonylphenol ethoxylates, and octylphenol ethoxylates.
  • a(n) amine ethoxylates, alkylaryl sulphonates, alkylbenzene sulphonates, castor oil ethoxylates and polyethylene glycol derivatives of hydrogenated castor oil, sorbitan fatty acid ester ethoxylates, sorbitan fatty acid esters, non-ionic ethoxylates, branched and unbranched secondary
  • the formulation when the formulation is a suspension concentrate, the formulation may comprise a wetting agent and a dispersing agent.
  • wetting agents are compounds that are used to prevent particles from clumping together before and during the milling process. Dispersants absorb to the surface of the milled particles to prevent flocculation and agglomeration. Examples of wetting agents include
  • ATLASTM G-5002L an exemplary polymeric emulsifier
  • ATLOXTM 4894 an exemplary nonionic surfactant blend
  • examples of dispersants include ATLOXTM 4913 LQ (a polymeric surfactant) and ATLOXTM Metasperse 500L (a polymeric dispersant solution). Wetting agents and dispersants may act via a steric or electronic mechanism.
  • Solid, particulate carriers that can be used, for example for dusts and dispersible powders, are kaolinite, lactose, calcite, talc, kaolin, diatomaceous earth, montmorillonite or attapulgite, highly-disperse silica or absorptive polymers.
  • Illustrative particulate, adsorptive carriers for granules include kaolinite, lactose, pumice, crushed brick, sepiolite or bentonite, montmorillonite-type clay, and exemplary nonsorbent carrier materials are calcite or dolomite.
  • a particulate solid formulation can also be prepared by encapsulation of a suitable mixture of fungicides, pesticides, or insecticides or by a granulation process that utilizes one or more of the above diluents or an organic diluent such as microcrystalline cellulose, rice hulls, wheat middlings, saw dust, and the like.
  • Illustrative granules can be prepared as discussed in US Patents No. 4,936,901, No. 3,708,573 and No. 4,672,065.
  • Suitable liquid carriers include: substituted aromatic hydrocarbons, in particular the fractions C 8 -C 12 , such as xylene mixtures or substituted naphthalenes, phthalic esters such as dibutyl or dioctyl phthalate, substituted aliphatic hydrocarbons such as limonene, alcohols and glycols as well as their ethers and esters, such as ethylene glycol monomethyl ether or benzyl alcohol, ketones such as cyclohexanone or isophorone, strongly polar solvents such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide, and, if appropriate, and epoxidized vegetable oils such as soybean oil.
  • the liquid carrier can be a naturally occurring essential oil, such as oils from citronella, castor, lemon, citrus fruits, and lemon grass. In a preferred embodiment, the liquid carrier is water.
  • a suspension concentrate formulation includes crystalline form A in an amount of about 15% by weight to about 70% by weight, in particular about 15% by weight to about 50% by weight, in particular about 20% by weight to about 50% by weight, in particular about 20% by weight to about 40% by weight.
  • an embodiment includes glycerin in an amount of about 2 to about 10% by weight, in particular about 5% by weight to about 10% by weight, in particular about 5% by weight.
  • an embodiment includes a wetting agent, such as ATLASTM G-5002L or ATLOXTM 4894, in an amount of about 0.2% by weight to about 5% by weight, in particular about 0.4% by weight to about 5% by weight, in particular about 0.4% by weight to about 2.5% by weight.
  • an embodiment includes a dispersing agent, such as ATLOXTM 4913 LQ or
  • Metasperse 500L in an amount of about 0.2% by weight to about 5% by weight, in particular about 0.4% by weight to about 5% by weight, in particular about 0.4% by weight to about 2.5% by weight.
  • an antifoaming agent such as MomentiveTM SAG30 or JT Baker Antifoam B silicone emulsion, in an amount of about 0.1% by weight.
  • an embodiment includes an antimicrobial agent, such as ProxcelTM or l,2-benzothiazol-3(2H)-one in an effective amount, in particular about 0.001% by weight to about 0.2% by weight, in particular 0.004% by weight to about 0.2% by weight, in particular 0.02% by weight to about 0.2% by weight, in particular about 0.06% by weight to about 0.2 % by weight, in particular 0.08% by weight to about 0.2% by weight.
  • an embodiment includes a thickening agent such as KelzanTM in an amount of about 0.1% by weight to 1.0% by weight.
  • a rheology modifier such as xanthan gum in an amount of about 0.1% by weight to about 1.0% by weight.
  • a suspension concentrate formulation includes crystalline form A with adjuvants that are favorable to agrochemical applications, including polysorbate, such as Tween 22, alkoxylated polyol ester, such as AtplusTM UEP-100, alkoxylated alcohol, such as AtplusTM PFA, methylated seed oil blend, such as AtplusTM MSO-HS 500, and blend of latex emulsion and trisiloane alkoxylate, such as Silwet Stik2.
  • polysorbate such as Tween 22
  • alkoxylated polyol ester such as AtplusTM UEP-100
  • alkoxylated alcohol such as AtplusTM PFA
  • methylated seed oil blend such as AtplusTM MSO-HS 500
  • blend of latex emulsion and trisiloane alkoxylate such as Silwet Stik2.
  • a contemplated formulation can also include at least one polymer that is a water-dispersible film-forming polymer that improves the adherence of at least the antimicrobial to the treated plant propagation material.
  • Suitable polymers include those known in the art for use in agrochemical compositions. Such compositions may also comprise a water soluble dye.
  • the formulations of the disclosure may further comprise suitable penetrants (adjuvants) to be applied in the present context.
  • suitable penetrants include substances, which are typically used in order to enhance the penetration of active agrochemical compounds into plants.
  • Penetrants in this context are able to penetrate the cuticle of the plant and thereby increase the mobility of the active compounds in the cuticle.
  • compositions comprising the crystalline form A of the present disclosure are preventively and/or curatively valuable in the field of pest control, even at low rates of application.
  • the crystalline form A of the disclosure and compositions of the disclosure have a favorable antimicrobial, particularly fungicidal, spectrum.
  • Compositions of the disclosure are particularly advantageous in that they may act against resistant fungi.
  • the present disclosure also encompasses a method of preventing or controlling a microbial infection on plants or plant propagation material comprising treating the plant or plant propagation material with an effective amount of a crystalline form of the compound of formula (I):
  • the present disclosure also encompasses a method of preventing or controlling fungal infection on plants or plant propagation material comprising treating the plant or plant propagation material with a fungicidally effective amount of a crystalline form of the compound of formula (I):
  • the present disclosure also encompasses a method of preventing or controlling microbial infection on plants or plant propagation material comprising treating the plant or plant propagation material with an effective amount of an agrochemical composition comprising a crystalline form of the compound of formula
  • the present disclosure also encompasses a method of preventing or controlling fungal infection on plants or plant propagation material comprising treating the plant or plant propagation material with a fungicidally effective amount of an agrochemical composition comprising a crystalline form of the compound of formula (I):
  • the agrochemical compositions comprising crystalline form A of the present disclosure may be used for the control of plant pathogenic microbes (e.g. fungi) on a number of plant species. Accordingly, the disclosure provides a method of preventing or controlling microbial (particularly fungal) infections on plants or plant propagation materials comprising treating the plant or plant propagation material with an antimicrobially effective amount of the agricultural composition of the disclosure. The disclosure also provides a method of preventing or controlling microbes on plants or plant propagation materials comprising treating the plant or plant propagation materials with the antimicrobially effective amount of the agricultural composition of the disclosure.
  • the crystalline form A is used in less than an antimicrobially effective amount. In some embodiments, the crystalline form A is used in less than a fungicidally effective amount. In these embodiments, the crystalline form A may be used in combination with other active ingredients. In some embodiments, this combination is synergistic.
  • the disclosed composition with favorable tolerance by plants, the environment, and favorable homeotherm toxicity is suitable for protecting plants and plant organs, increasing harvest yields, and improving the quality of the harvested material. It is preferred in its application as crop protection composition. It is active against normally sensitive and resistant species and against all or some stages of development.
  • the rate at which the agrochemical compositions of the disclosure are applied will depend upon the particular type of microbes (particularly fungi) to be controlled, the degree of control required, and the timing and method of application and can be readily determined by the person skilled in the art.
  • the agricultural composition of the disclosure may further comprise at least one further active ingredient selected from the group consisting of: a second fungicide, a nematicide, an insecticide, and a second antimicrobial, or any
  • the at least one further active ingredient is a second fungicide.
  • further active ingredients include agronomic chemicals such as bactericides and herbicides, as well as plant nutrients and plant fertilizers.
  • agronomic chemicals such as bactericides and herbicides, as well as plant nutrients and plant fertilizers.
  • the present disclosure enables the use of a composition together with one or more pesticides, plant nutrients, or plant fertilizers.
  • the combination may encompass specific plant traits incorporated into the plant using any means such as conventional breeding or genetic modification.
  • a particular aspect of the disclosure involves the agrochemical composition comprising crystalline form A and a second fungicide.
  • the agrochemical composition comprises crystalline form A and a second fungicide in a synergistic mixture.
  • compositions comprising crystalline form A and other active substances may have other surprising advantages which can be described as synergistic activity, better tolerance by plants, reduced phytotoxicity, increased anti-fungal activity, overall decreased pesticide use, and/or better behavior relating to production such as grinding, mixing, storage or use.
  • the fungicide has a preselected mode of action as described by the FRAC Target Site Code.
  • the preselected FRAC Target Site Code is selected from the group consisting of: Bl, B3, C2, C3, C4, C6, Dl, El, E2, E3, Gl, H5, M4, and M5.
  • the second fungicide is selected from one or more of the group consisting of: carbendazim, thiabendazole, thiophanate, thiophanate-methyl, diethofencarb, zoxamide, ethaboxam, pencycuron, fluopicolide, metrafenone, pyriofenone, flutolanil, fluopyram, fluxapyroxad, penthiopyrad, benodanil, mepronil, isofetamid, fenfuram, carboxin, oxycarboxin, thifluzamide, benzovindiflupyr, bixafen, furametpyr, inpyrfluxam, isopyrazam, penflufen, sedaxane, isoflucypram, pydiflumetofen, pyraziflumid, boscalid, benomyl, fuberid
  • tetraconazole triadimefon, triadimenol, triticonazole, prothioconazole, aldimorph, dodemorph, fenpropimorph, tridemorph, fenpropidin, spiroxamine, fenhexamid, fenpyrazamine, piperalin, pyributicarb, naftifme, terbinafme, validamycin, polyoxin, dimethomorph, flumorph, pyrimorph, benthiavalicarb, iprovalicarb, valifenalate, mandipropamid, copper, sulphur, ferbam, mancozeb, maneb, metiram, propineb, thiram, zineb, zinc thiazole, ziram, captan, captafol, folpet, dichlofluanid, tolylfluanid, chlorothalonil, chlozolinate, dimethach
  • the mixing partners may exist in the form of any suitable
  • the crystalline form of the disclosure can be used to control one or more target microbes or prevent the growth of one or more target microbes.
  • the agrochemical composition of the disclosure can be used to control one or more target microbes or prevent the growth of one or more target microbes.
  • the crystalline form of the disclosure can be used to control one or more target fungi or prevent the growth of one or more target fungi. Accordingly, the agrochemical composition of the disclosure can be used to control one or more target fungi or prevent the growth of one or more target fungi.
  • the crystalline form of the disclosure can exhibit outstanding efficacy against a broad spectrum of phytopathogenic fungi, including soil borne pathogens, which are in particular members of the classes Plasmodiophoromycetes,
  • fungicides are systemically active and can be used in plant protection as foliar, seed dressing or soil fungicide. Furthermore, they are suitable for combating fungi, which, inter alia, infest wood or roots of plant.
  • target fungi include: one or more members of the phyla of Ascomycota, Oomycota, Basidiomycota, and the subphylum Mucoromycotina.
  • the target fungi of the division Ascomycota include, for example, subdivision Pezizomycotina and Taphrinomycotina which include Dothideomycetes, Leotiomycetes, Sordariomycetes and Taphrinomycetes classes.
  • the target fungi of the division Basidiomycota include, for example, subdivisions Agaricomycotina, Pucciniomycotina, and Ustilaginomycotina.
  • the one or more target fungi whose growth is to be controlled or inhibited is selected from one or more of the group consisting of Alternaria, Aspergillus, Bipolaris, Blumeria, Botrytis, Candida, Cercospora,
  • Pyrenophora Pyricularia, Pythium, Rhizoctonia, Sclerophthora, Sclerotinia, Septoria, Setosphaeria, Stangospora, Uncinula, Ustilago, Venturia, Verticillium, and Zymoseptoria.
  • the compound of formula (II) can be prepared by heating the compound of formula (I) under vacuum or by exposing the compound of formula (I) to dehydrating conditions.
  • the compound of formula (II) is advantageous in that it reverts to the compound of formula (I) once it is exposed to water.
  • Plants that are treated in accordance with the disclosure include the following plants: maize, soya bean, alfalfa, cotton, sunflower, Brassica oil seeds such as Brassica napus (e.g. canola, rapeseed), Brassica rapa, B.juncea (e.g. field mustard), Brassica carinata, Arecaceae sp. (e.g. oilpalm, coconut, rice, wheat, sugar beet, sugar cane, oats, rye, barley, millet and sorghum, triticale, flax, nuts, grapes and vine and various fruit and vegetables from various botanic taxa), Rosaceae sp. (e.g.
  • pome fruits such as apples and pears, but also stone fruits such as apricots, cherries, almonds, plums, peaches, and berry fruits such as strawberries, raspberries, red and black currant, and gooseberry), Ribesioidae sp., Juglandaceae sp., Betulaceae sp., Anacardiaceae sp., Fagaceae sp., Moraceae sp., Oleaceae sp. (e.g. olive tree), Actinidaceae sp., Lauraceae sp. (e.g. avocado, cinnamon, camphor), Mtisaceae sp. (e.g.
  • Rubiaceae sp. e.g. coffee
  • Theaceae sp. e.g. tea
  • Sterculiceae sp. e.g. tea
  • Rutaceae sp. e.g. lemons, oranges, mandarins, and grapefruit
  • Solanaceae sp. e.g. tomatoes, potatoes, peppers, capsicum, aubergines, tobacco
  • Liliaceae sp. Compositae sp.
  • Umbelliferae sp. e.g. carrots, parsley, celery and celeriac
  • Cucurbitaceae sp. e.g. cucumbers— including gherkins, pumpkins, watermelons, calabashes and melons
  • Alliaceae sp. e.g. leeks and onions
  • Cucurbitaceae sp.
  • Cruciferae sp. e.g. white cabbage, red cabbage, broccoli, cauliflower, Brussels sprouts, pak choi, kohlrabi, radishes, horseradish, cress and Chinese cabbage
  • Leguminosae sp. e.g. peanuts, peas, lentils, and beans such as common beans and broad beans
  • Chenopodiaceae sp. e.g. Swiss chard, fodder beet, spinach, beetroot
  • Linaceae sp. e.g. hemp
  • Cannabeacea sp. e.g. cannabis
  • Malvaceae sp. e.g. okra, cocoa
  • Papaveraceae e.g. poppy
  • Asparagaceae e.g. asparagus
  • useful plants and ornamental plants in the garden and woods including turf, lawn, grass, and Stevia rebaudiana In each case it also includes genetically modified types of these plants.
  • Rosaceae sp. e.g. pome fruits such as apples and pears, but also stone fruits such as apricots, cherries, almonds, plums and peaches, and berry fruits such as strawberries, raspberries, red and black currant and gooseberry
  • Rosaceae sp. e.g. pome fruits such as apples and pears, but also stone fruits such as apricots, cherries, almonds, plums and peaches, and berry fruits such as strawberries, raspberries, red and black currant and gooseberry
  • Ribesioidae sp. Juglandaceae sp.
  • Betulaceae sp. Anacardiaceae sp.
  • Fagaceae sp. Moraceae sp.
  • Oleaceae sp. e.g.
  • Actinidaceae sp. Lauraceae sp. (e.g. avocado, cinnamon, camphor), Musaceae sp. (e.g. banana trees and plantations), Rubiaceae sp. (e.g. coffee), Theaceae sp. (e.g. tea), Sterculiceae sp., Rutaceae sp. (e.g. lemons, oranges, mandarins and grapefruit); Solanaceae sp. (e.g. tomatoes, potatoes, peppers, capsicum, aubergines, tobacco), Liliaceae sp., Compositae sp. (e.g.
  • lettuce artichokes and chicory such as root chicory, endive or common chicory
  • Umbelliferae sp. e.g. carrots, parsley, celery and celeriac
  • Cucurbitaceae sp. e.g. cucumber including gherkins, pumpkins, watermelons, calabashes and melons
  • Alliaceae sp. e.g. leeks and onions
  • Cruciferae sp. e.g. white cabbage, red cabbage, broccoli, cauliflower, Brussels sprouts, pak choi, kohlrabi, radishes, horseradish, cress and Chinese cabbage
  • Leguminosae sp. e.g.
  • plants which can be treated in accordance with the disclosure are tomatoes.
  • plants can be protected against attack by the designated pathogens within a certain period of time after the treatment.
  • the period of time within which protection is effected extends from 1 to up to 14 days, preferably 1 to 7 days, after the treatment of the plants.
  • intensity ratio Ka2/Ka1 intensity ratio Ka2/Ka1 :
  • TGA data were collected using a TA Q5000/5500 TGA from TA Instruments.
  • DSC was performed using a TA Q2000/2500 DSC from TA Instruments. The detailed parameters used are listed in Table 1.3.
  • the starting material was characterized by X-ray powder diffraction (XRPD), thermo gravimetric analysis (TGA), differential scanning calorimetry (DSC), dynamic vapor sorption (DVS), high performance liquid chromatography (HPLC), and 'H solution nuclear magnetic resonance ('H NMR).
  • XRPD X-ray powder diffraction
  • TGA thermo gravimetric analysis
  • DSC differential scanning calorimetry
  • DFS dynamic vapor sorption
  • HPLC high performance liquid chromatography
  • 'H NMR 'H solution nuclear magnetic resonance
  • Type A 0.5 142.7 Anhydrate Form A
  • XRPD (FIG. 1 A) revealed that the starting material was crystalline and was named as Type A. ETpon comparison of the XRPD patterns for the starting sample in reflection and transmission modes, several additional diffraction peaks (-23°, -25°, -28°, -33°) were clearly observed on the transmission pattern. This difference was postulated to be caused by preferred orientation, since the morphology of Type A starting material was rod-like. TGA and DSC data are shown in Fig. 1B. A two-stage weight loss of 0.5% up to 100 °C and 10.0% from 100 °C to 160 °C was observed on the TGA curve.
  • the DSC result exhibited one sharp endotherm at 142.7 °C (onset temperature).
  • the DVS isotherm plot of Type A was collected at 25 °C between 0 and 95%RH. As displayed in Fig. 2A, a water up-take of 0.1% was observed at 25
  • Example 3.6 Slurry at 50 °C
  • Polymer mixture A polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), polyvinylchloride (PVC), polyvinyl acetate (PVAC), hypromellose (HPMC), methyl cellulose (MC) (mass ratio of 1 : 1 : 1 : 1 : 1).
  • Polymer mixture B polycaprolactone (PCL), polyethylene glycol (PEG), polymethyl methacrylate (PMMA) sodium alginate (SA), and hydroxy ethyl cellulose (ELEC) (mass ratio of 1 : 1 : 1 : 1 : 1).
  • Example 3.13 Crystallization with the Presence of Cations
  • Crystallization experiments in the presence of cations were performed under 3 conditions, using NaCl, KC1 and AlCb. Control experiments using the same solvent and amount of chloride salt (without addition of (I)) were also set up in
  • Type A is an anhydrate.
  • the crystal structure of the single crystal sample was determined by single-crystal X-ray diffraction (SCXRD) successfully.
  • the crystal system is triclinic and the space group is R ⁇ .
  • Further crystallographic data and the refinement parameters are listed below in Table 4.1.1.
  • the asymmetric unit of the single crystal is comprised of only one benzoxaborole molecule, which indicates that the single crystal is an anhydrate of the benzoxaborole (FIG 19A).
  • the thermal ellipsoid drawing of Type A in the crystal lattice is shown in FIG. 19B.
  • the single crystal structure determination confirms the chemical structure of (I) in the crystal.
  • the unit cell of the single crystal is shown in FIG 20A. demonstrating that each unit cell contains two (I) molecules.
  • the classic hydrogen bonds in the single crystal structure are shown in FIG 20B and the classic hydrogen bonding parameters are listed in Table 4.1.2.
  • the calculated and experimental XRPD patterns of this single crystal are consistent with experimental XRPD of Type A reference as shown in FIG. 21 A.
  • a suitable single crystal with good diffraction quality was selected and was wrapped with Paratone-N (an oil based cryoprotectant).
  • the crystal was mounted on a mylar loop in a random orientation and immersed in a stream of nitrogen at 175 K.
  • Preliminary examination and data collection were performed on a Bruker D8
  • the anisotropic displacement factor exponent ta ces the form: -2 2 [h 2 a* 2 Un + 2hka*b*Ui2 +— ].
  • Example 4 The single crystal structure determination results in Example 4 demonstrated that (I) of Type A is an anhydrate, while a weight loss of 10.0% from 100 °C to 160 °C was observed on the TGA curve. To investigate this TGA weight loss, additional experiments were performed.
  • (I) has a benzoxaborole group, which may undergo a dehydration reaction under elevated temperature as shown below:
  • the TGA weight loss may be associated with the dehydration reaction shown above, where the compound of formula (II) is a product.
  • variable-temperature XRPD (VT-XRPD) and heating experiments were performed.
  • the XRPD overlay displayed in FIG. 22A indicated that a partial conversion to the dehydrated product (II) occurred after being heated to 160 °C and cooled to RT (when exposed to air).
  • 'H NMR and TGA were also performed for the samples before and after heating.
  • the 3 ⁇ 4 NMR results in FIG 22B show no difference before and after heating, likely because the dehydrated product converted back to (I) after being exposed to residual water in DMSO-t/i.
  • TGA was also performed by heating (I) to 160 °C and cooling to room temperature, followed by re-heating to 160 °C after placed being placed under ambient conditions overnight.
  • the results in FIG. 23 A showed a similar weight loss was still observed for the re-heated sample. All the results were consistent with the hypothesis that dehydration and hydration reactions would occur during heating and exposure to air, respectively.
  • cycle TGA was conducted by heating Type A to 160 °C and cooling to 50 °C (with N2 purge, without exposure to air), followed by re-heating to 160 °C.
  • the results in FIG. 24A indicated that a weight loss of 1.3% up to 150 °C was still observed on the re-heating curve, which was postulated to be decomposition/sublimation rather than dehydration.
  • Isothermal TGA was conducted by heating Type A to 160 °C and isothermal at 160 °C for 0.5 hr. A weight loss of >20% was observed during the isothermal stage FIG. 24B, which was postulated to be decomposition/sublimation.
  • a suspension concentrate formulation was prepared using the following reagents and procedure:
  • a suspension concentrate formulation was prepared using the following reagents and the procedure detailed in Example 7:
  • the SC formulation were visually monitored for stability after it was stored at; 5°C, 20°C, or 50°C for 10 days.
  • the formulations were then diluted in water and analyzed with a Malvern 3000E to determine particle size.
  • the 50°C sample demonstrated hard sedimentation and settling of active ingredient but little to no change was noted for the samples that were stored at 5°C or 20°C.
  • Particle size analysis of the diluted SC formulations are shown in the Table below. The form is believed to be crystalline form A. The data shows that the particle size of the SC formulations did not change under any of the storage conditions, demonstrating that the solid form and corresponding SC formulation are favorable for agrochemical applications.
  • a suspension concentrate formulation was prepared using the following reagents and the procedure detailed in Example 7:
  • a suspension concentrate formulation was prepared using the following reagents and the procedure detailed in Example 7:
  • the SC formulation was visually monitored for stability when it was stored at: 5°C, 20°C, or 50°C, each for 10 days. Following storage, the formulations were then diluted in water analyzed with a Malvern 3000E to determine particle size. Visually, the sample displayed little to no change over the 10 days at; 5°C, 20°C, or 50°C . Particle size analysis of the diluted SC formulations are shown in the Table below. The form is believed to be crystalline form A. The data shows that the particle size of the SC formulations did not change under any storage conditions, demonstrating that the solid form and corresponding SC formulation are favorable for agrochemical applications.
  • a suspension concentrate formulation was prepared using the following reagents and the procedure detailed in Example 7:
  • Example 12 Suspension Concentrate Formulation Preparation and Stability (Unconfirmed) [00247] A suspension concentrate formulation was prepared using the following reagents and the procedure detailed in Example 7:
  • the SC formulation was visually monitored for stability when it was stored at; 5°C, 20°C, or 50°C for 10 days.
  • the formulations were then diluted in water analyzed with a Malvern 3000E to determine particle size.
  • the sample displayed little to no change over the 10 days at; 5°C, 20°C, or 50°C
  • the data shows that the particle size of the SC formulations did not change under 5°C and 20°C storage conditions. A particle size change was noticed in the 50°C storage condition after 10 days.
  • the form is believed to be crystalline form A.
  • Example 11 23 mg of this suspension concentrate, which was believed to be crystalline form A, was then added to 0.26 g of water, followed by 78 mg of Florite 1706 Plantability Polymer and 36 mg of Keystone 610-548-25; the resulting mixture was gently shaken to produce a sample of formulation suitable for treating seeds. The formulation was added to 100 g of soybean seeds in a tumbler seed treater.
  • a sample suspension concentrate was prepared as described in
  • Example 11 The form is believed to be crystalline form A. 46 mg of this suspension concentrate was then added to 0.26 g of water, followed by 78 mg of Florite 1706 Plantability Polymer and 36 mg of Keystone 610-548-25; the resulting mixture was gently shaken (to produce a sample of formulation suitable for treating seeds). The formulation was added to 100 g of soybean seeds in a tumbler seed treater.
  • Example 15 Suspension Concentrate for Seed Treatment Formulation and Germination Studies (Unconfirmed) [00253] A sample suspension concentrate was prepared as described in
  • Example 11 The form is believed to be crystalline form A. 70 mg of this suspension concentrate was then added to 0.26 g of water, followed by 78 mg of Florite 1706 Plantability Polymer and 36 mg of Keystone 610-548-25; the resulting mixture was gently shaken (to produce a formulation suitable for treating seeds).
  • the formulation was added to 100 g of soybean seeds in a tumbler seed treater.
  • the treated seeds were planted in small pots of soil to test germination. Germination results were recorded after 7 days; as illustrated below, the treated seeds germinated at a rate of 95%, which is similar to the untreated seeds germination rate of 98%.
  • the data shows that an SC based seed treatment did not affect germination rates of the seeds in a significant way, and therefor is a favorable formulation type for agrochemical application.
  • Example 16 Suspension Concentrate for Seed Treatment Formulation and Germination Studies (Unconfirmed) [00255] A sample suspension concentrate was prepared as described in
  • Example 11 The form is believed to be crystalline form A. 0.14 g of this suspension concentrate was then added to 0.26 g of water, followed by 78 mg of Florite 1706 Plantability Polymer and 36 mg of Keystone 610-548-25; the resulting mixture was gently shaken (to produce a formulation suitable for treating seeds).
  • the formulation was added to 100 g of soybean seeds in a tumbler seed treater.
  • the treated seeds were planted in small pots of soil to test germination. Germination results were recorded after 7 days; as illustrated below, the treated seeds germinated at a rate of 95% which is similar to the untreated seeds germination rate of 98%.
  • the data shows that an SC based seed treatment did not affect germination rates of the seeds in a significant way, and therefore is a favorable formulation type for agrochemical application.
  • a suspension concentrate formulation was prepared using the following reagents and procedure:
  • Benzisothiazol-3(2H)-one and hand mixing to create a slurry.
  • the beads were removed by filtration and the thickener mixture was mixed with the milled mixture with a high shear mixer.
  • the solid form of (I) was analyzed by XRPD before and after milling/formulation to determine if the solid form was sufficiently stable to remain unchanged during the milling and formulation process.
  • the suspension concentrate sample was prepared for XRPD analysis by centrifugation at 12000 RPM for 10 minutes. The resulting wet cake was then analyzed by XRPD.
  • a suspension concentrate formulation was prepared using the following reagents and the procedure detailed in Example 17:
  • the SC formulation was visually monitored for stability when it was stored at; 5°C, 20°C, or 50°C for 10 days. After storage, the formulations were diluted in water analyzed with a Malvern 3000E to determine particle size and a VWR pH meter to determine pH. Visually, the sample displayed little to no change over the 10 days at 5°C, 20°C, or 50°C. The data shows that the particle size of the SC
  • formulations did not change under 5°C storage conditions. A particle size change was noticed in the 20°C and 50°C storage condition after 10 days. Tinder all three storage conditions at 10 days, the change in pH was minimal.
  • a suspension concentrate formulation was prepared using the following reagents and procedure:
  • the water was mixed using a low shear mixer.
  • the wetting agent was then added to the mixture, followed by the dispersant and antifoam.
  • (I) (crystalline form A) was then added slowly portion-wise.
  • the resulting suspension was then added to a Union Process Atritor Bead Mill system, and the suspension was bead milled for 1.5 - 2 hours or until (I) had reached the desired particle size.
  • the thickener mixture was prepared by first adding the xanthan gum to glycerin, then adding the l,2-benzisothiazol- 3(2H)-one and hand mixing to create a slurry. When the milling was complete, the beads were removed by filtration and the thickener mixture was mixed with the milled mixture with a high shear mixer.
  • Example 20 Suspension Concentrate Formulation Preparation and Stability A suspension concentrate formulation was prepared using the following reagents and the procedure detailed in Example 19:
  • the SC formulation was visually monitored for stability when it was stored at; 5°C, 20°C, or 50°C for 10 days.
  • the formulations were then diluted in water and analyzed with a Malvern 3000E to determine particle size and a VWR pH meter to determine pH.
  • the sample displayed little to no change over the 10 days at 5°C, 20°C, or 50°C.
  • the data shows that the particle size of the SC formulations did not change under 20°C storage conditions. A particle size change was noticed in the 5°C and 50°C storage condition after 10 days. Under all three storage conditions at 10 days, the change in pH was minimal.
  • a milling slurry was prepared using the following reagents and procedure:
  • a suspension concentrate formulation was prepared using the following reagents and the procedure detailed in Example 17:
  • the solid form of (I) was analyzed by XRPD before and after milling/formulation to determine if the solid form was sufficiently stable to remain unchanged during the milling and formulation process.
  • the suspension concentrate sample was prepared for XRPD analysis by centrifugation at 12000 RPM for 10 minutes.
  • the resulting wet cake was then analyzed by XRPD.
  • the results are shown in Figures 30B, 31 A and 31B.
  • the XRPD results showed that the solid form is crystalline form A before and after milling/formulation (all the samples conformed to Type A), indicating that crystalline form A is a favorable crystalline form to use for further SC development.
  • a suspension concentrate formulation was prepared using the following reagents and the procedure detailed in Example 17:
  • a suspension concentrate formulation was prepared using the following reagents and the procedure detailed in Example 17:
  • SC was prepared, .9 mL of SC was aliquoted into 5 mL vials to test compatibility and stability with various adjuvants.
  • the SC and adjuvant samples were prepared as follows; first, 0.1 mL of adjuvant was added directly to the vial containing the SC and vortexed for 1 minute to well combine. Atplus UEP-100 needed to be heated to 50°C before being added to the SC, which was also heated to 50°C, to compatibilize the adjuvant before vortexing.
  • the SC formulations were visually monitored for stability when it was stored at 5 °C, 20 °C, or 50 °C for 10 days. The each of the formulations were then diluted in water and analyzed with a Malvern 3000E to determine particle size and with a VWR pH meter to determine pH.
  • the sample displayed little to no change over the 10 days at 5 °C, 20 °C, or 50 °C. Tinder all three storage conditions at 10 days, the change in pH was minimal.
  • a suspension concentrate formulation was prepared using the following reagents and the procedure detailed in Example 19:
  • SC was prepared, .9 mL of SC was aliquoted into 5 mL vials to test compatibility and stability with various adjuvants. For each test, 0.1 mL of adjuvant was added directly to the vial containing the SC and vortexed for 1 minute to well combine. Atplus UEP-100 needed to be heated to 50°C before being added to the SC, which had also been heated to 50°C, to compatibilize the adjuvant before vortexing. The SC formulations were visually monitored for stability when it was stored at 5 °C, 20 °C, or 50 °C for 10 days.

Abstract

La présente invention concerne des formes solides d'un composé de benzoxaborole substitué, spécifiquement des formes cristallines d'un composé de formule (I), des compositions comprenant des formes cristallines du composé de formule (I), et leurs méthodes d'utilisation.
PCT/US2019/047073 2018-08-18 2019-08-19 Formes solides de benzoxaborole substitué et compositions associées WO2020041200A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
AU2019325436A AU2019325436B2 (en) 2018-08-18 2019-08-19 Solid forms of substituted benzoxaborole and compositions thereof
EP19852023.1A EP3836938A4 (fr) 2018-08-18 2019-08-19 Formes solides de benzoxaborole substitué et compositions associées
CA3148168A CA3148168A1 (fr) 2018-08-18 2019-08-19 Formes solides de benzoxaborole substitue et compositions associees
CN201980067966.8A CN112867494A (zh) 2018-08-18 2019-08-19 取代苯并氧杂硼杂环戊烯的固体形式和其组合物
JP2021532287A JP2021534247A (ja) 2018-08-18 2019-08-19 置換ベンゾキサボロールの固体形態およびその組成物
MX2021001904A MX2021001904A (es) 2018-08-18 2019-08-19 Formas solidas de benzoxaborol sustituido y composiciones de las mismas.
BR112021003037-9A BR112021003037A2 (pt) 2018-08-18 2019-08-19 formas sólidas de benzoxaborol substituído e composições do mesmo

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201862719632P 2018-08-18 2018-08-18
US62/719,632 2018-08-18

Publications (1)

Publication Number Publication Date
WO2020041200A1 true WO2020041200A1 (fr) 2020-02-27

Family

ID=69523717

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2019/047073 WO2020041200A1 (fr) 2018-08-18 2019-08-19 Formes solides de benzoxaborole substitué et compositions associées

Country Status (9)

Country Link
US (4) US11236115B2 (fr)
EP (1) EP3836938A4 (fr)
JP (1) JP2021534247A (fr)
CN (1) CN112867494A (fr)
AU (1) AU2019325436B2 (fr)
BR (1) BR112021003037A2 (fr)
CA (1) CA3148168A1 (fr)
MX (1) MX2021001904A (fr)
WO (1) WO2020041200A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021158595A1 (fr) * 2020-02-05 2021-08-12 Agrofresh Inc. Composés et compositions antimicrobiens

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111655035A (zh) 2017-11-30 2020-09-11 博瑞金股份有限公司 苯并氧杂硼杂环戊烯化合物和其制剂
AU2019325436B2 (en) 2018-08-18 2023-10-26 5Metis, Inc. Solid forms of substituted benzoxaborole and compositions thereof

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3708573A (en) 1969-03-15 1973-01-02 Kumiai Chemical Industry Co Agricultural and horticultural granule formulation and methods for preparing the same and for using thereof
US4672065A (en) 1982-11-19 1987-06-09 Chevron Research Company N-substituted phenoxyacetamide fungicides
US4936901A (en) 1986-07-09 1990-06-26 Monsanto Company Formulations of water-dispersible granules and process for preparation thereof
WO1997033890A1 (fr) 1996-03-11 1997-09-18 Novartis Ag Derives de pyrimidine-4-one utilises comme pesticide
US5880188A (en) 1994-06-09 1999-03-09 Zeneca Limited Oxaboroles and salts thereof, and their use as biocides
US20060234981A1 (en) * 2005-02-16 2006-10-19 Anacor Pharmaceuticals Boron-containing small molecules
US20120214765A1 (en) * 2008-03-06 2012-08-23 Anacor Pharmaceuticals, Inc. Boron-containing small molecules as anti-inflammatory agents
WO2016128949A1 (fr) 2015-02-12 2016-08-18 Glaxosmithkline Intellectual Property (No.2) Limited Composés benzoxaborole et leurs utilisations
WO2016164589A1 (fr) 2015-04-09 2016-10-13 The Penn State Research Foundation Composition antifongicide contenant du benzoxaborole
US20170037258A1 (en) * 2015-08-06 2017-02-09 Stephen J. Benkovic Benzoxaborole-Containing Coating Resistant To Cellulose-Supportable Fungus
US9617285B2 (en) 2013-03-15 2017-04-11 Eli Lilly And Company 1-hydroxy-benzooxaboroles as antiparasitic agents

Family Cites Families (88)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4038741A1 (de) 1990-12-05 1992-06-11 Bayer Ag Mittel zum schutz von pflanzen gegen befall durch mikroorganismen
AU683177B2 (en) 1994-06-20 1997-10-30 Premacs International Pty Limited Method for the treatment of seeds with betaines
AUPN229595A0 (en) 1995-04-12 1995-05-04 Eastman Kodak Company Integrated drive circuitry in lift print heads
ATE364705T1 (de) 1997-04-03 2007-07-15 Dekalb Genetics Corp Verwendung von glyphosat-resistente maislinien
US6333449B1 (en) 1998-11-03 2001-12-25 Plant Genetic Systems, N.V. Glufosinate tolerant rice
WO2000026356A1 (fr) 1998-11-03 2000-05-11 Aventis Cropscience N. V. Riz tolerant au glufosinate
EP1366070A2 (fr) 2000-10-25 2003-12-03 Monsanto Technology LLC Mecanisme biochimique de plant de coton pv-ghgt07(1445), compositions et techniques de detection de celui-ci
US6818807B2 (en) 2001-08-06 2004-11-16 Bayer Bioscience N.V. Herbicide tolerant cotton plants having event EE-GH1
KR100454531B1 (ko) 2002-05-25 2004-11-05 기영상 미끄럼 방지용 타포린 및 그 제조방법
EP1532247A4 (fr) 2002-07-29 2006-08-30 Monsanto Technology Llc Mais pv-zmir13 designe mon863, composition et procedes de detection
GB0225129D0 (en) 2002-10-29 2002-12-11 Syngenta Participations Ag Improvements in or relating to organic compounds
JP2006508680A (ja) 2002-12-05 2006-03-16 モンサント　テクノロジー　エルエルシー コヌカグサ事象ａｓｒ−３６８ならびにその検出のための組成物および方法
US7381861B2 (en) 2003-02-12 2008-06-03 Monsanto Technology Llc Cotton event MON 88913 and compositions and methods for detection thereof
WO2004074492A1 (fr) 2003-02-20 2004-09-02 Kws Saat Ag Betteraves sucrieres tolerant le glyphosate
WO2005054480A2 (fr) 2003-12-01 2005-06-16 Syngenta Participations Ag Plants de coton resistant aux insectes et procedes de detection de ces derniers
US7157281B2 (en) 2003-12-11 2007-01-02 Monsanto Technology Llc High lysine maize compositions and event LY038 maize plants
HUE025703T2 (en) 2003-12-15 2016-04-28 Monsanto Technology Llc MON88017 corn plant and compositions, and a method for detecting them
JP2007530036A (ja) 2004-03-25 2007-11-01 シンジェンタ パーティシペーションズ アクチェンゲゼルシャフト Ｍｉｒ６０４系統トウモロコシ
EP2333082B1 (fr) 2004-03-26 2015-01-07 Dow AgroSciences LLC Lignées de coton transgéniques Cry1F et Cry1AC et leur identification spécifique à l'événement
US7767657B2 (en) 2005-02-16 2010-08-03 Anacor Pharmaceuticals, Inc. Boron-containing small molecules
MX2007012383A (es) 2005-04-08 2007-11-07 Bayer Bioscience Nv Evento elite a2704-12 y metodos y equipos para identificar dicho evento en muestras biologicas.
DK1871901T3 (da) 2005-04-11 2011-10-17 Bayer Bioscience Nv Elitebegivenhed A5547-127 samt fremgangsmåder og sæt til identifikation af en sådan begivenhed i biologiske prøver
WO2006128569A2 (fr) 2005-06-02 2006-12-07 Syngenta Participations Ag Coton insecticide 1143-14a
US20100024077A1 (en) 2005-06-02 2010-01-28 Syngenta Participations Ag Ce44-69d insecticidal cotton
EP1917359A2 (fr) 2005-06-02 2008-05-07 Syngeta Participations AG Coton insecticide transgenique ce43-67b exprimant cry1ab
WO2006128570A1 (fr) 2005-06-02 2006-12-07 Syngenta Participations Ag Coton insecticide 1143-51b
BRPI0614338B1 (pt) 2005-08-08 2018-01-02 Bayer Cropscience Nv Processos para a identificação de um evento elite em amostras biológicas, para a confirmação da pureza das sementes, para a seleção de sementes em relação à presença do dito evento elite, para a determinação do status de zigosidade de uma planta, material de planta ou semente que compreende o dito evento elite, para detecção da presença do dito evento elite, e para a produção de uma planta ou de uma semente de algodão que compreende o dito evento elite, bem como kits para a identificação do dito evento elite, par de iniciadores adequado para uso na detecção específica do mesmo, e sonda específica para a identificação do dito evento elite
BRPI0615088A2 (pt) 2005-08-24 2009-07-14 Pioneer Hi Bred Int composições que fornecem toleráncia a herbicidas múltiplos e métodos de uso das mesmas
ES2400809T3 (es) 2005-08-31 2013-04-12 Monsanto Technology Llc Secuencias de nucleótidos que codifican proteínas insecticidas
WO2011066360A1 (fr) 2009-11-24 2011-06-03 Dow Agrosciences Llc Détection de l'événement 416 du soja aad-12
CN101421404A (zh) 2006-02-10 2009-04-29 马哈拉施特拉杂交种子有限公司 表达cry1ac基因的转基因茄子(solanum melongena)
RU2642628C2 (ru) 2006-02-16 2018-01-25 Анакор Фармасьютикалз, Инк. Бор-содержащие малые молекулы в качестве противовоспалительных средств
JP2009536660A (ja) 2006-05-02 2009-10-15 アナコール ファーマシューティカルズ，インコーポレイテッド 加水分解耐性ホウ素含有治療剤及びその使用方法
EP2021476B1 (fr) 2006-05-26 2014-07-09 Monsanto Technology, LLC Plant et semence de maïs correspondant au produit transgénique mon89034, procédés de détection et utilisation associés
EA021187B1 (ru) 2006-06-03 2015-04-30 Зингента Партисипейшнс Аг Хромосомный целевой сайт кукурузы и способ получения трансгенной кукурузы
US20070286822A1 (en) 2006-06-12 2007-12-13 Anacor Pharmaceuticals Inc. Compounds for the Treatment of Periodontal Disease
FR2905195B1 (fr) 2006-08-23 2008-10-10 Dav Sa Module de commande, en particulier pour vehicule automobile
EP2066789A4 (fr) 2006-09-29 2009-12-30 Anacor Pharmaceuticals Inc Structure cristalline d'une arnt synthetase
US7928296B2 (en) 2006-10-30 2011-04-19 Pioneer Hi-Bred International, Inc. Maize event DP-098140-6 and compositions and methods for the identification and/or detection thereof
JO3396B1 (ar) 2007-06-20 2019-10-20 Anacor Pharmaceuticals Inc جزيئات صغيرة تحتوي على البورون
EP2209897A1 (fr) 2007-11-15 2010-07-28 Monsanto Technology, LLC Plante et graine de soja correspondant à l'événement transgénique mon87701 et procédés pour les détecter
WO2009100188A2 (fr) 2008-02-08 2009-08-13 Dow Agrosciences Llc Procédés de détection de l’événement de maïs das-59132
KR101597376B1 (ko) 2008-02-15 2016-02-26 몬산토 테크놀로지 엘엘씨 트랜스제닉 계통 ｍｏｎ８７７６９에 상응하는 대두 식물 및 종자, 및 그의 검출 방법
PL2247736T3 (pl) 2008-02-29 2013-10-31 Monsanto Technology Llc Zdarzenie MON87460 rośliny kukurydzy oraz kompozycje i sposoby do jego wykrywania
EP2187893A4 (fr) 2008-03-06 2012-02-22 Anacor Pharmaceuticals Inc Petites molécules contenant du bore utilisées en tant qu'agents anti-inflammatoires
BRPI0910402A2 (pt) 2008-04-08 2015-07-28 Basf Se Formulação de concentrado emulsificável, processo para preparar um concentrado emulsificável, uso de um concentrado emulsificável, e, método para controlar fungos nocivos.
WO2010024976A1 (fr) 2008-08-29 2010-03-04 Monsanto Technology Llc Plante et semences de soja correspondant à l’événement transgénique mon87754 et procédés pour détection de celui-ci
CA2738474C (fr) 2008-09-29 2020-05-12 Monsanto Technology Llc Evenement transgenique de soja t mon87705 et procedes pour la detection de celui-ci
MX346321B (es) 2008-12-16 2017-03-15 Syngenta Participations Ag Evento 5307 del maiz.
WO2010110400A1 (fr) 2009-03-26 2010-09-30 武田薬品工業株式会社 Composé hétérocyclique
WO2010117737A1 (fr) 2009-03-30 2010-10-14 Monsanto Technology Llc Evénement de riz transgénique 17053 et ses procédés d'utilisation
WO2010117735A1 (fr) 2009-03-30 2010-10-14 Monsanto Technology Llc Évènement 17314 de riz transgénique et ses procédés d'utilisation
CA2771538C (fr) 2009-08-19 2019-06-04 Dow Agrosciences Llc Evenement das-40278-9 d'aad-1, lignees transgeniques de mais connexes et identification specifique d'evenement de celui-ci
CN102596984A (zh) 2009-09-17 2012-07-18 孟山都技术公司 大豆转基因事件mon 87708及其使用方法
WO2011060199A1 (fr) 2009-11-11 2011-05-19 Anacor Pharmaceuticals, Inc. Petites molecules contenant du bore
UA115762C2 (uk) 2009-11-23 2017-12-26 Монсанто Текнолоджи Ллс Рекомбінантна молекула днк, яка вказує на присутність трансгенної події mon 87427 маїсу
UA113610C2 (xx) 2009-11-24 2017-02-27 Рослина трансгенної сої, яка включає подію 416 сої aad-12
US20110154525A1 (en) 2009-12-17 2011-06-23 Pioneer Hi-Bred International, Inc. Maize event DP-040416-8 and methods for detection thereof
WO2011075595A1 (fr) 2009-12-17 2011-06-23 Pioneer Hi-Bred International, Inc. Maïs dp-043a47-3 et procédés de détection associés
HRP20211762T1 (hr) 2010-09-07 2022-02-18 Anacor Pharmaceuticals, Inc. Derivati benzoksaborola za liječenje bakterijskih infekcija
BR112014008186A2 (pt) 2011-10-07 2017-04-11 Syngenta Participations Ag método para proteção de plantas úteis ou material de propagação de plantas
US11039617B2 (en) 2013-01-30 2021-06-22 Agrofresh Inc. Large scale methods of uniformly coating packaging surfaces with a volatile antimicrobial to preserve food freshness
US9585396B2 (en) 2013-01-30 2017-03-07 Agrofresh Inc. Volatile applications against pathogens
US11766043B2 (en) 2013-01-30 2023-09-26 Agrofresh Inc. Vaporized administration of pesticides
US8669207B1 (en) 2013-01-30 2014-03-11 Dow Agrosciences, Llc. Compounds and compositions
US10070649B2 (en) 2013-01-30 2018-09-11 Agrofresh Inc. Volatile applications against pathogens
JP5927686B1 (ja) 2013-01-30 2016-06-01 アグロフレッシュ インコーポレイテッド 食肉、植物または植物の一部分に対する揮発性抗菌剤としてのベンゾオキサボロールの使用
WO2014173880A1 (fr) 2013-04-22 2014-10-30 Syngenta Participations Ag Nouveaux microbiocides
AU2014202928B1 (en) 2013-06-05 2014-09-11 Agrofresh Inc. Compounds and compositions
US20170000133A1 (en) 2013-12-23 2017-01-05 Syngenta Participations Ag Benzoxaborole fungicides
JP2015212249A (ja) 2014-05-05 2015-11-26 アナコール ファーマシューティカルズ，インコーポレイテッド 化合物および爪光沢剤
AU2015259744B2 (en) 2014-05-12 2020-04-30 Agrofresh Inc. Volatile applications against pathogens
EP2982247A1 (fr) 2014-08-07 2016-02-10 Omya International AG Produit antiseptique, son procédé de préparation et son utilisation
LT3221308T (lt) 2014-11-21 2018-12-27 F2G Limited Priešgrybeliniai agentai
BR112017014839A2 (pt) 2015-01-13 2018-06-19 Syngenta Participations Ag novos microbicidas
AR103397A1 (es) 2015-01-13 2017-05-10 Syngenta Participations Ag Oxoborazoles microbicidas
BR112017017197B1 (pt) 2015-02-12 2022-07-19 Agrofresh Inc. Composto e seus métodos de preparação e de uso contra patógenos que afetam carnes, plantas, ou partes de plantas, bem como mistura ou composição compreendendo o dito composto
CN105712969B (zh) 2016-01-27 2018-07-27 杭州科巢生物科技有限公司 维帕他韦中间体的合成方法
US10435419B2 (en) 2016-04-18 2019-10-08 Biophore India Pharmaceuticals Pvt. Ltd. Process for the preparation of tavaborole, its novel polymorphic forms and the polymorphs thereof
US20180009831A1 (en) 2016-07-06 2018-01-11 Apicore Us Llc Process for the preparation of novel polymorphic forms of 5-fluoro-1,3-dihydro-1-hydroxy-2,1- benzoxaborole
WO2018060140A1 (fr) * 2016-09-27 2018-04-05 Syngenta Participations Ag Dérivés de benzoxaboroles microbiocides
WO2019108879A1 (fr) 2017-11-30 2019-06-06 Boragen, Inc. Compositions combinatoires de benzoxaboroles et d'agents biologiques
CN111655035A (zh) 2017-11-30 2020-09-11 博瑞金股份有限公司 苯并氧杂硼杂环戊烯化合物和其制剂
WO2019152641A1 (fr) 2018-02-01 2019-08-08 Boragen, Inc. Compositions de benzoxaborole ayant un effet d'amélioration de la croissance
AU2019325436B2 (en) 2018-08-18 2023-10-26 5Metis, Inc. Solid forms of substituted benzoxaborole and compositions thereof
WO2020123881A1 (fr) 2018-12-12 2020-06-18 Boragen, Inc. Composés contenant du bore et leurs utilisations
CN111233908A (zh) 2019-02-21 2020-06-05 南京农业大学 苯并氧杂硼-1-醇类化合物及其制备方法和应用
WO2021021932A1 (fr) 2019-07-30 2021-02-04 Boragen, Inc. Procédé de réaction d'écoulement pour la fabrication de produits agrochimiques contenant du bore

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3708573A (en) 1969-03-15 1973-01-02 Kumiai Chemical Industry Co Agricultural and horticultural granule formulation and methods for preparing the same and for using thereof
US4672065A (en) 1982-11-19 1987-06-09 Chevron Research Company N-substituted phenoxyacetamide fungicides
US4936901A (en) 1986-07-09 1990-06-26 Monsanto Company Formulations of water-dispersible granules and process for preparation thereof
US5880188A (en) 1994-06-09 1999-03-09 Zeneca Limited Oxaboroles and salts thereof, and their use as biocides
WO1997033890A1 (fr) 1996-03-11 1997-09-18 Novartis Ag Derives de pyrimidine-4-one utilises comme pesticide
US20060234981A1 (en) * 2005-02-16 2006-10-19 Anacor Pharmaceuticals Boron-containing small molecules
US20120214765A1 (en) * 2008-03-06 2012-08-23 Anacor Pharmaceuticals, Inc. Boron-containing small molecules as anti-inflammatory agents
US9617285B2 (en) 2013-03-15 2017-04-11 Eli Lilly And Company 1-hydroxy-benzooxaboroles as antiparasitic agents
WO2016128949A1 (fr) 2015-02-12 2016-08-18 Glaxosmithkline Intellectual Property (No.2) Limited Composés benzoxaborole et leurs utilisations
WO2016164589A1 (fr) 2015-04-09 2016-10-13 The Penn State Research Foundation Composition antifongicide contenant du benzoxaborole
US20160324160A1 (en) 2015-04-09 2016-11-10 Stephen Benkovic Synergistic benzoxaborole-containing anti-fungicidal composition
US20170037258A1 (en) * 2015-08-06 2017-02-09 Stephen J. Benkovic Benzoxaborole-Containing Coating Resistant To Cellulose-Supportable Fungus

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
"The Pesticide Manual", 2009, BRITISH CROP PROTECTION COUNCIL
"U.S. Environmental Protection Agency, Office of Pesticide Programs", 1998, U.S. GOVERNMENT PRINTING OFFICE
BAUR ET AL., PESTICIDE SCIENCE, vol. 51, 1997, pages 131 - 152
See also references of EP3836938A4
ZHDANKIN V V: "TETRAHYDRON LETTERS", vol. 40, 10 September 1999, ELSEVIER, article "Synthesis and structure of benzoboroxoles: novel organoboron heterocycles", pages: 6705 - 6708

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021158595A1 (fr) * 2020-02-05 2021-08-12 Agrofresh Inc. Composés et compositions antimicrobiens

Also Published As

Publication number Publication date
US20230159565A1 (en) 2023-05-25
EP3836938A1 (fr) 2021-06-23
CN112867494A (zh) 2021-05-28
US11560393B2 (en) 2023-01-24
US11066424B2 (en) 2021-07-20
AU2019325436B2 (en) 2023-10-26
EP3836938A4 (fr) 2022-05-11
BR112021003037A2 (pt) 2021-05-11
US11236115B2 (en) 2022-02-01
AU2019325436A1 (en) 2021-03-18
JP2021534247A (ja) 2021-12-09
CA3148168A1 (fr) 2020-02-27
US20200055878A1 (en) 2020-02-20
MX2021001904A (es) 2021-05-27
US20210221827A1 (en) 2021-07-22
US20200239497A1 (en) 2020-07-30

Similar Documents

Publication Publication Date Title
US11560393B2 (en) Solid forms of substituted benzoxaborole and compositions thereof
JP6539205B2 (ja) ピコリン酸誘導体を含んでなる相乗性植物病害防除用組成物
JP2013166724A (ja) フルミオキサジンの結晶形
CN102459256A (zh) 一种偶氮环酰胺的固体形式
UA127448C2 (uk) Рідкий фунгіцидний склад на масляній основі
CN105308025A (zh) 杀真菌吡唑的固体形式
CN105829306A (zh) 2-{3-[2-(1-{[3,5-双(二氟甲基)-1h-吡唑-1-基]乙酰基}哌啶-4-基)-1,3-噻唑-4-基]-4,5-二氢-1,2-噁唑-5-基}-3-氯苯基甲磺酸酯的新晶形
BR112021008755A2 (pt) misturas e composições contendo 5-fluoro-4-imino-3- metil-1-tosil-3,4-dihidropirimidina-2-ona, e métodos de uso.
CN112739210A (zh) 杀真菌组合物
CN116096237A (zh) 杀真菌混合物
CN110881476A (zh) 高效广谱低毒环保农用新化合物及其组合物
CN116113623A (zh) 包含5-氟-4-亚氨基-3-甲基-1-甲苯磺酰基-3,4-二氢嘧啶-2-酮的混合物及组合物，及其使用方法
BR112020010927A2 (pt) compostos de benzoxaborol e formulações dos mesmos
CN111333594A (zh) 广谱杀菌低毒低残留叶青双新化合物及其组合物
WO2022001047A1 (fr) Dérivé de quinoléine phénol ou sel à activité pesticide acceptable de celui-ci, composition et utilisation associée
CN115067348A (zh) 一种复配组合物及其在农业中的应用
JP2013256478A (ja) フルミオキサジンの結晶形
CN111548293A (zh) 广谱杀菌低毒低残留促生长硫菌灵锰锌化合物及其组合物
CN111423472A (zh) 广谱杀菌低毒低残留促生长噻森锰锌化合物及其组合物
CN111631223A (zh) 广谱杀菌低毒促生长甲基硫菌灵金属复合物及其组合物
CN111187234A (zh) 广谱杀菌无公害促生长噻唑锰化合物及其组合物
CN115039784B (zh) 一种组合物及其在农业中的应用
CN117545743A (zh) 5-氟-4-亚氨基-3-甲基-1-甲苯磺酰基-3,4-二氢嘧啶-2-酮的晶型以及其混合物、组合物和使用方法
WO2023135535A1 (fr) Mélanges fongicides comprenant une combinaison contenant des fongicides de phtalimide
CN115067345A (zh) 一种杀菌组合物、制剂及其应用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19852023

Country of ref document: EP

Kind code of ref document: A1

DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
ENP Entry into the national phase

Ref document number: 2021532287

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112021003037

Country of ref document: BR

ENP Entry into the national phase

Ref document number: 2019325436

Country of ref document: AU

Date of ref document: 20190819

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2019852023

Country of ref document: EP

Effective date: 20210318

ENP Entry into the national phase

Ref document number: 112021003037

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20210218

ENP Entry into the national phase

Ref document number: 3148168

Country of ref document: CA